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J Immunol. 2014 Aug 1;193(3):1373-82. doi: 10.4049/jimmunol.1400145. Epub 2014 Jun 25.

Integrin-mediated first signal for inflammasome activation in intestinal epithelial cells.

Author information

1
Department of Microbiology and Immunology, University of Texas Health Science Center, San Antonio, TX 78229; and.
2
Department of Microbiology and Immunology, University of Texas Health Science Center, San Antonio, TX 78229; and Center for Airway Inflammation Research, University of Texas Health Science Center, San Antonio, TX 78229.
3
Department of Microbiology and Immunology, University of Texas Health Science Center, San Antonio, TX 78229; and Center for Airway Inflammation Research, University of Texas Health Science Center, San Antonio, TX 78229 Dube@uthhscsa.edu.

Abstract

How intestinal epithelial cells (IECs) recognize pathogens and activate inflammasomes at intestinal surfaces is poorly understood. We hypothesized that IECs use integrin receptors to recognize pathogens and initiate inflammation within the intestinal tract. We find that IECs infected with Yersinia enterocolitica, an enteric pathogen, use β1 integrins as pathogen recognition receptors detecting the bacterial adhesin invasin (Inv). The Inv-integrin interaction provides the first signal for NLRP3 inflammasome activation with the type three secretion system translocon providing the second signal for inflammasome activation, resulting in release of IL-18. During infection, Yersinia employs two virulence factors, YopE and YopH, to counteract Inv-mediated integrin-dependent inflammasome activation. Furthermore, NLRP3 inflammasome activation in epithelial cells requires components of the focal adhesion complex signaling pathway, focal adhesion kinase, and rac1. The binding of Inv to β1 integrins rapidly induces IL-18 mRNA expression, suggesting integrins provide a first signal for NLRP3 inflammasome activation. These data suggest integrins function as pathogen recognition receptors on IECs to rapidly induce inflammasome-derived IL-18-mediated responses.

PMID:
24965773
PMCID:
PMC4174679
DOI:
10.4049/jimmunol.1400145
[Indexed for MEDLINE]
Free PMC Article

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